1. Field of the Invention
The invention relates to the field of the aseptic transfer of biopharmaceutical products between a container and a closed chamber.
More specifically, a first aspect of the invention concerns a leaktight joining device specially intended for the aseptic transfer of products belonging to the biopharmaceutical field, between a container and a closed chamber. The invention also relates, according to a second aspect, to an assembly comprising a container, such a leaktight joining device, and a chamber, in order to ensure the aseptic transfer of biopharmaceutical products between the container and the closed chamber. The invention further relates, in a third aspect, to a method for the aseptic transfer of a biopharmaceutical product between the container and the closed chamber.
2. Description of the Related Art
The term “biopharmaceutical product” or “biopharmacy product” is understood here to mean that which is related to biotechnology, pharmacy, and more generally to the medical field. In particular, a biopharmaceutical product is a product originating from biotechnology—culture media, cell cultures, buffer solutions, artificial nutrition liquids—or a product intended to be used in the pharmaceutical or medical field, at least in part, as a more or less finely divided solid, as a liquid, or as a paste, or, more generally, a physical product—cap, vessel, integrated ports or tube, syringe, syringe plunger, functional processing or packaging means, a more or less complex assembly comprising a plurality of products, etc.—intended for use inside the closed chamber.
By convention, the terms “container” or “containing” mean that which, in biopharmacy, is able to and is designed for containing, enclosing, or holding in its interior a specific biopharmaceutical content or where appropriate several biopharmaceutical contents, in a static manner that is more or less lasting or permanent. Such biopharmaceutical contents typically consist of one or more biopharmaceutical product(s) as defined above. Such containers may be rigid or flexible, reusable or disposable, of various sizes, for example bags, sleeves, containers, vessels, bioreactors, or spouts for biopharmaceutical use, this not being an exhaustive list.
In the field of aseptic transfers of biopharmaceutical products, there is a need for establishing a connection between a container and a sealed chamber in order to transfer biopharmaceutical products without breaking the seal of the chamber and/or container relative to the outside environment as this could result in contamination of the biopharmaceutical products.
To do this, the “Biosafe Monolever Port 110” is known from the prior art—according to the preamble of claim 1—which relates to a leaktight joining device for ensuring such an aseptic transfer. This joining device comprises stationary temporary clamping means formed by a first annular ring gear rotatable about a geometric axis and actuating, via the displacement of a pushbutton causing this first annular ring gear to rotate, axial clamping elements for holding the container against the door of the chamber. The joining device also comprises stationary locking and unlocking means, arranged on the wall of the chamber and allowing the container to transition from an initial locking position where a removable cover seals the container, to an intermediate unlocking position where the removable cover is detached from the container and is held against the door of the chamber to form a seal for the aseptic transfer of biopharmaceutical products. These stationary locking and unlocking means consist of a second annular ring gear, rotatable about a geometric axis of rotation coinciding with the geometrical axis of the first annular ring gear and movable by manipulation of a lever. The movement of the lever in one direction rotates the annular ring gear in this direction and thus unlocks the removable cover from the container, while the movement of the lever in the other direction rotates the annular ring gear in the opposite direction and thus once again locks the removable cover against the container.
Such a construction has several disadvantages. First, the operation of clamping the container against the door of the chamber, on the one hand, and the operations of locking and unlocking the removable cover on the container, on the other hand, are performed by different actuation means—the pushbutton and the lever—which are independent of each other, which implies additional manufacturing costs and does not follow the general trend of simplification of the joining device. Also, the manipulation of such a joining device, although relatively simple, can sometimes result in complications because the operator must first move the pushbutton to ensure the container is clamped against the door of the chamber, then must move the lever in a first direction to unlock the removable cover from the container, and finally must move the lever in another direction to lock the removable cover against the container once again. These three independent actions must be carried out successively and at irregular time intervals, which is not intuitive and may cause voluntary or involuntary operator errors. Seals may then be compromised, both within the chamber and the containers, contaminating the biopharmaceutical products. Furthermore, such a plurality of actuation means causes numerous difficulties in automating this type of joining device.
Also known are the prior art documents EP-A1-0688020 and EP-A1-1141974 relating to a technology similar to that described above but where the joining device does not have an annular ring gear. The stationary clamping means and stationary unlocking/locking means are therefore actuated differently and via mechanisms that are structurally and functionally independent of each other.
Besides the drawbacks mentioned above, this solution involves the manipulation of three independent levers for locking and unlocking the removable cover of the container, arranged on the periphery of the chamber door. This increases the risk of manipulation errors, as well as increasing the at-risk areas where loss of integrity is likely to occur within the closed chamber or container.
Also known, from prior art document WO-A1-2010/054031, is a leaktight joining device having stationary locking/unlocking means similar to those described for the above documents. However, this leaktight joining device is usable with containers having built-in locking/unlocking means positioned directly on the periphery of the annular flange. These built-in locking/unlocking means are formed by several parts which can be manipulated independently of each other and are reversibly movable from a position in which they are introduced only into the flange of the container—the removable cover then being free—to a position where they are introduced simultaneously into the flange of the container and into the removable cover—the latter then being held in position so as to seal the container.
Such an embodiment also has several disadvantages. Firstly, the presence of several pins for removably locking the cover on the container, which can be moved independently of each other, does not ensure optimum reliability concerning loss of integrity of the joining device. Instead there is a high probability that manipulation of these different pins. In the specific movements required for locking and unlocking the removable cover, will lead to human error likely to cause failure in the internal isolation of the container or chamber. Secondly, the use of such manually movable pins causes accelerated wear on the equipment which must therefore be replaced more regularly. Thirdly, it should be noted that, as above, automation of such a system is particularly complex and therefore costly.
Document WO2010/054031 discloses a container intended for the aseptic transfer of a product to a chamber. The container comprises an annular flange defining an opening, and a removable cover is provided.
Document FR 2872446 discloses a double-door leaktight transfer device for performing a leaktight transfer between a first sealed chamber, for example a containment cell, and a second sealed chamber, for example a transfer box, comprising two doors each equipped with means for locking it to a flange having a central opening and an actuator for actuating the locking means, the actuators being rotatably mounted in the doors and comprising a peephole.
GB 2 218 663 discloses a double-lidded system comprising a first cylindrical container, open at one end, a first lid for the first container, means defining a port for a second container, and a second lid for said port, the first container having a peripheral seal for sealing to the port and to the first lid, and the second lid having a peripheral seal for sealing to the port and to the first lid, wherein the first lid comprises a catch mechanism of a first rotary element for securing the first lid to the first container, the first container incorporating engagement means for cooperating with the catch mechanism of the first rotary element, the second lid incorporates a rotary drive shaft extending through it and means for rotating the shaft are provided, and a catch mechanism of the second rotary element which can be actuated by the shaft to secure the first lid to the second lid, the first lid comprising means with which the catch mechanism of the second rotary element can engage, the system lastly incorporating a clutch teeth mechanism with at least twenty teeth which are engaged when the first lid is adjacent to the second lid such that rotation of the shaft causes simultaneous rotation of the first and second rotary catch mechanisms.
GB 2,102,719 discloses a system for bringing hazardous materials in and out of an enclosure, such as a glovebox, through a port in a wall of the enclosure. The port is normally closed by a door which cooperates with a removable end closure on a container or the like when the latter is presented to and secured to the port. The container is secured in position at the port by means of a rotatable coupling ring. A locking device ensures that the door cannot be opened in the absence of a container at the port and also that the container cannot be removed from the port when the door is open. Instead of the container, a glove secured to a rigid sleeve may be used to allow the operator to perform a work function within the glovebox.